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The purpose of this study is to evaluate the pharmacokinetics and safety of oral posaconazole tablets in Chinese participants at high risk for invasive fungal infections. Neutropenic participants undergoing chemotherapy for acute myelogenous leukemia or myelodysplastic syndromes will be enrolled in the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Posaconazole | Experimental | Posaconazole 300 mg tablet (3 x 100 mg tablets) once every 12 hours on Day 1 and once-daily on Days 2 to 28 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Posaconazole | Drug | Posaconazole 300 mg solid oral tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Steady-state Average Concentration (ssCavg) of Posaconazole on Day 8 | The ssCavg was calculated in order to determine the percentage of participants achieving the pharmacokinetic (PK) target of ssCavg >500 ng/mL on Day 8 when plasma drug levels had reached steady state. | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8 |
| Steady-state Area Under the Concentration-time Curve (ssAUC0-24hr) of Posaconazole on Day 8 | The ssAUC0-24hr was calculated to determine the mean plasma drug concentration in the Intensive and Sparse PK subgroup from immediately after dosing to 24 hours post-dose on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean). | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8 |
| Steady-state Maximum Concentration (ssCmax) of Posaconazole on Day 8 | The ssCmax was calculated in order to determine the maximum post-dose plasma drug concentration in the Intensive and Sparse PK subgroup on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean). | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8 |
| Steady-state Minimum Concentration (ssCmin) of Posaconazole on Day 8 | The ssCmin was calculated in order to determine the lowest measurable drug concentration in the Intensive and Sparse PK subgroup up to 24 hours post-dose on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean). | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8 |
| Time to Steady-state Maximum Concentration (ssTmax) of Posaconazole on Day 8 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32319040 | Derived | Liu K, Wu D, Li J, Chen H, Ning H, Zhao T, Dai H, Chen L, Mangin E, Winchell GA, Waskin H, Jiang J, Qiu Y, Zhao XM. Pharmacokinetics and Safety of Posaconazole Tablet Formulation in Chinese Participants at High Risk for Invasive Fungal Infection. Adv Ther. 2020 May;37(5):2493-2506. doi: 10.1007/s12325-020-01341-x. Epub 2020 Apr 22. |
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Adult (18 to 70 years of age) male and female participants with neutropenia undergoing chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) were recruited at 4 sites in China.
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| ID | Title | Description |
|---|---|---|
| FG000 | Posaconazole | All participants received posaconazole 300 mg tablet (3 x 100 mg tablets) once every 12 hours on Day 1 and once-daily on Days 2 to 28. The first 20 participants (Intensive and Sparse PK subgroup) underwent intensive and sparse pharmacokinetic (PK) sampling on Days 1 and 8; the next 45 participants (Sparse PK subgroup) underwent PK sampling on Day 8 only. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Posaconazole | All participants received posaconazole 300 mg tablet (3 x 100 mg tablets) once every 12 hours on Day 1 and once-daily on Days 2 to 28. The first 20 participants (Intensive and Sparse PK subgroup) underwent intensive and sparse pharmacokinetic (PK) sampling on Days 1 and 8; the next 45 participants (Sparse PK subgroup) underwent PK sampling on Day 8 only. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Steady-state Average Concentration (ssCavg) of Posaconazole on Day 8 | The ssCavg was calculated in order to determine the percentage of participants achieving the pharmacokinetic (PK) target of ssCavg >500 ng/mL on Day 8 when plasma drug levels had reached steady state. | The PK analysis set included all randomized and treated participants who complied with the protocol and have documented adherence to daily dosing and PK regimens through the Day 8 steady-state evaluation and have data available. | Posted | Number | Percentage of Participants | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8 |
|
Up to Day 42
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MK-5592 | All participants received posaconazole 300 mg tablet (3 x 100 mg tablets) once every 12 hours on Day 1 and once-daily on Days 2 to 28. The first 20 participants (Intensive and Sparse group) underwent intensive and sparse PK sampling on Days 1 and 8; the next 45 participants (Sparse group) underwent PK sampling on Day 8 only. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anal infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D009181 | Mycoses |
| ID | Term |
|---|---|
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C101425 | posaconazole |
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The ssTmax was calculated in order to determine the amount of time required to reach ssCmax in the Intensive and Sparse PK subgroup on Day 8. |
| Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8 |
| AUC0-24hr of Posaconazole on Day 1 | The AUC0-24hr was calculated to determine the mean plasma drug concentration from immediately after dosing to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean). | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 |
| Cmax of Posaconazole on Day 1 | The Cmax was calculated to determine the maximum plasma drug concentration up to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean). | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 |
| Cmin of Posaconazole on Day 1 | The Cmin was calculated in order to determine the lowest measurable drug concentration from immediately after dosing to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean). | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 |
| Tmax of Posaconazole on Day 1 | The Tmax was calculated in order to determine the time required to reach Cmax in the Immediate and Sparse PK subgroup on Day 1. | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Primary | Steady-state Area Under the Concentration-time Curve (ssAUC0-24hr) of Posaconazole on Day 8 | The ssAUC0-24hr was calculated to determine the mean plasma drug concentration in the Intensive and Sparse PK subgroup from immediately after dosing to 24 hours post-dose on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean). | The PK analysis set included all randomized and treated participants in the Intensive and Sparse PK subgroup who complied with the protocol and have documented adherence to daily dosing and PK regimens through the Day 8 steady-state evaluation and have data available. | Posted | Mean | Standard Deviation | hr*ng/mL | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8 |
|
|
|
| Primary | Steady-state Maximum Concentration (ssCmax) of Posaconazole on Day 8 | The ssCmax was calculated in order to determine the maximum post-dose plasma drug concentration in the Intensive and Sparse PK subgroup on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean). | The PK analysis set included all randomized and treated participants in the Intensive and Sparse PK subgroup who complied with the protocol and have documented adherence to daily dosing and PK regimens through the Day 8 steady-state evaluation with available data. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8 |
|
|
|
| Primary | Steady-state Minimum Concentration (ssCmin) of Posaconazole on Day 8 | The ssCmin was calculated in order to determine the lowest measurable drug concentration in the Intensive and Sparse PK subgroup up to 24 hours post-dose on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean). | The PK analysis set included all randomized and treated participants in the Intensive and Sparse subgroup who complied with the protocol and have documented adherence to daily dosing and PK regimens through the Day 8 steady-state evaluation with available data. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8 |
|
|
|
| Primary | Time to Steady-state Maximum Concentration (ssTmax) of Posaconazole on Day 8 | The ssTmax was calculated in order to determine the amount of time required to reach ssCmax in the Intensive and Sparse PK subgroup on Day 8. | The PK analysis set included all randomized and treated participants in the Intensive and Sparse PK subgroup who complied with the protocol and have documented adherence to daily dosing and PK regimens through the Day 8 steady-state evaluation with available data. | Posted | Median | Full Range | hr | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8 |
|
|
|
| Primary | AUC0-24hr of Posaconazole on Day 1 | The AUC0-24hr was calculated to determine the mean plasma drug concentration from immediately after dosing to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean). | The PK analysis set included all randomized and treated participants in the Intensive and Sparse PK subgroup who complied with the protocol and have documented adherence to daily dosing and PK regimens through the Day 8 steady-state evaluation with available data. | Posted | Mean | Standard Deviation | hr*ng/mL | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 |
|
|
|
| Primary | Cmax of Posaconazole on Day 1 | The Cmax was calculated to determine the maximum plasma drug concentration up to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean). | The PK analysis set included all randomized and treated participants in the Immediate and Sparse PK subgroup who complied with the protocol and have documented adherence to daily dosing and PK regimens through the Day 8 steady-state evaluation with available data. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 |
|
|
|
| Primary | Cmin of Posaconazole on Day 1 | The Cmin was calculated in order to determine the lowest measurable drug concentration from immediately after dosing to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean). | The PK analysis set included all randomized and treated participants in the Intensive and Sparse PK subgroup who complied with the protocol and have documented adherence to daily dosing and PK regimens through the Day 8 steady-state evaluation with available data. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 |
|
|
|
| Primary | Tmax of Posaconazole on Day 1 | The Tmax was calculated in order to determine the time required to reach Cmax in the Immediate and Sparse PK subgroup on Day 1. | The PK analysis set included all randomized and treated participants in the Intensive and Sparse PK subgroup who complied with the protocol and have documented adherence to daily dosing and PK regimens through the Day 8 steady-state evaluation with available data. | Posted | Median | Full Range | Hours | Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 |
|
|
|
| 4 |
| 65 |
| 64 |
| 65 |
| Lung infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Haemorrhage intracranial | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Faeces hard | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Febrile infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Soft tissue infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Transfusion related complication | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 19.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 19.0 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 19.0 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Hypoproteinaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation.